The Optimal Cut-off of BIPSS in Differential Diagnosis of ACTH-dependent Cushing’s Syndrome: Is Stimulation Necessary?

Abstract

Abstract Contexts Bilateral inferior petrosal sinus sampling (BIPSS) can differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS). The traditional cutoff of inferior petrosal sinus to peripheral (IPS:P) ACTH gradient was 2 before stimulation and 3 after stimulation, which yielded unsatisfactory sensitivity in some studies. Objectives To determine the optimal cutoff in BIPSS before or after desmopressin stimulation and to evaluate the necessity of stimulation. Design and Setting Single-center retrospective study (2011–2018) along with meta-analysis. Patients 226 CD and 24 EAS patients with confirmed diagnosis who underwent BIPSS with desmopressin stimulation. Results In the meta-analysis of 25 studies with 1249 CD and 152 EAS patients, the traditional cutoff yielded sensitivity of 86% and 97% and specificity of 98% and 100% before and after stimulation, respectively. We then analyzed the data from our center. With the traditional cutoff, the sensitivity was 87.2% (197/226) and 96.5% (218/226) before and after stimulation, and specificity was both 100% (25/25), which were close to the results of meta-analysis. Receiver operating characteristic analysis revealed that the optimal cutoff was 1.4 before stimulation and 2.8 after stimulation. With the new cutoff, the sensitivity was 94.7% (214/226) and 97.8% (221/226) while the specificity remained 100% (25/25) before and after stimulation. Among the 7 CD patients (7/226; 3.1%) for whom stimulation was necessary to get correct diagnosis, none has a pituitary lesion >6 mm by magnetic resonance imaging, and their sampling lateralization rate (P = .007) and peak ACTH level at dominant inferior petrosal sinus (P = .011) were lower than those among CD patients with IPS:P >1.4 before stimulation. Conclusions The optimal cutoff for IPS:P in BIPSS is different from the commonly-used one. The optimal cutoff value can yield satisfactory accuracy even without stimulation, and stimulation may be unnecessary for those with pituitary adenoma >6 mm.